Design of targeted, capture-based, next generation sequencing tests for precision cancer therapy

  • Author Footnotes
    1 Equal contribution.
    Ian S. Hagemann
    Correspondence
    Corresponding author.
    Footnotes
    1 Equal contribution.
    Affiliations
    Genomics and Pathology Services, Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
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  • Author Footnotes
    1 Equal contribution.
    Catherine E. Cottrell
    Footnotes
    1 Equal contribution.
    Affiliations
    Genomics and Pathology Services, Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
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  • Author Footnotes
    1 Equal contribution.
    Christina M. Lockwood
    Footnotes
    1 Equal contribution.
    Affiliations
    Genomics and Pathology Services, Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
    Search for articles by this author
  • Author Footnotes
    1 Equal contribution.
      In cancer medicine, next generation sequencing (NGS) has emerged as a practical method to generate patient- and tumor-specific genetic data for optimal selection of targeted therapies. Targeted sequencing allows clinical testing to focus on cancer-related genes, thus maximizing the test’s sensitivity and specificity for actionable variants. In this review, we summarize the current regulatory environment surrounding clinical NGS, including regulations and professional opinions established by the College of American Pathologists, the Centers for Disease Control and Prevention, the Clinical Laboratory Improvement Amendments, the Clinical and Laboratory Standards Institute, the Association for Molecular Pathology, the New York State Department of Health, and the American College of Medical Genetics. We outline practical considerations for the design of targeted NGS assays, with an emphasis on capture-based methods. Finally, we discuss components of the validation process for clinical NGS assays as well as challenges that still remain for clinical NGS.

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      References

        • Gargis A.S.
        • Kalman L.
        • Berry M.W.
        • et al.
        Assuring the quality of next generation sequencing in clinical laboratory practice.
        Nat Biotechnol. 2012; 30: 1033-1036
      1. College of American Pathologists. Molecular pathology checklist. Available at: http://www.cap.org/apps/docs/laboratory_accreditation/checklists/new/molecular_pathology_checklist.pdf. Accessed on June, 28, 2013.

        • Clinical and Laboratory Standards Institute
        Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine; Approved Guideline. CLSI document MM9-A.
        Clinical and Laboratory Standards Institute, Wayne, Pennsylvania2004
      2. New York State Department of Health. “Next Generation” Sequencing (NGS) Guidelines for Somatic Genetic Variant Detection. Available at: http://www.wadsworth.org/labcert/TestApproval/forms/NextGenSeq_ONCO_Guidelines.pdf. Accessed on June, 28, 2013.

        • Schrijver I.
        • Aziz N.
        • Farkas D.H.
        • et al.
        Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.
        J Mol Diagn. 2012; 14: 525-540
        • Richards C.S.
        • Bale S.
        • Bellissimo D.B.
        • et al.
        Molecular Subcommittee of the ALQAC. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007.
        Genet Med. 2008; 10: 294-300
        • Hadd A.G.
        • Houghton J.
        • Choudhary A.
        • et al.
        Targeted, high-depth, next generation sequencing of cancer genes in formalin-fixed, paraffin-embedded and fine-needle aspiration tumor specimens.
        J Mol Diagn. 2013; 15: 234-247
        • Pritchard C.C.
        • Smith C.
        • Salipante S.J.
        • et al.
        ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing.
        J Mol Diagn. 2012; 14: 357-366
        • Mamanova L.
        • Coffey A.J.
        • Scott C.E.
        • et al.
        Target-enrichment strategies for next generation sequencing.
        Nat Methods. 2010; 7: 111-118
        • Bainbridge M.N.
        • Wang M.
        • Burgess D.L.
        • et al.
        Whole exome capture in solution with 3 Gbp of data.
        Genome Biol. 2010; 11: R62
        • Gnirke A.
        • Melnikov A.
        • Maguire J.
        • et al.
        Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing.
        Nat Biotechnol. 2009; 27: 182-189
      3. Ernani FP, LeProust EM. Agilent’s SureSelect target enrichment system: bringing cost and process efficiency to next generation sequencing. Available at: http://www.chem.agilent.com/Library/brochures/5990-3532en_lo%20CMS.pdf. Accessed on May, 21, 2013.

        • Sulonen A.M.
        • Ellonen P.
        • Almusa H.
        • et al.
        Comparison of solution-based exome capture methods for next generation sequencing.
        Genome Biol. 2011; 12: R94
      4. Life Technologies. Ion TargetSeq custom enrichment kits: user guide. Available at: http://tools.lifetechnologies.com/content/sfs/manuals/IonTargetSeq_Custom_UG.pdf. Accessed on November, 6, 2013.

        • Kohlmann A.
        • Grossmann V.
        • Haferlach T.
        Integration of next generation sequencing into clinical practice: are we there yet?.
        Semin Oncol. 2012; 39: 26-36
        • Azuara D.
        • Ginesta M.M.
        • Gausachs M.
        • et al.
        Nanofluidic digital PCR for KRAS mutation detection and quantification in gastrointestinal cancer.
        Clin Chem. 2012; 58: 1332-1341
        • Forshew T.
        • Murtaza M.
        • Parkinson C.
        • et al.
        Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA.
        Sci Transl Med. 2012; 4: 136ra68
        • Mertes F.
        • Elsharawy A.
        • Sauer S.
        • et al.
        Targeted enrichment of genomic DNA regions for next generation sequencing.
        Brief Funct Genomics. 2011; 10: 374-386
      5. Fluidigm Corporation. Sequencing: from sample to sequence ready. Available at: http://www.fluidigm.com/home/fluidigm/images/products/access_array_final_post.pdf. Accessed on November, 6, 2013.

      6. RainDance Technologies. RainDance ThunderStorm System [product brief]. Available at: http://www.raindancetech.com/rdt/wp-content/uploads/downloads/product-brief_thunderstorm.pdf. Accessed on November, 6, 2013.

      7. De Witte A, Ashutosh, Le Cocq C, et al. Agilent HaloPlex Target Enrichment System: design and analysis of clinical research panels [application note]. Available at: http://www.chem.agilent.com/library/applications/5991-1919EN_2-4-13Low.pdf. Accessed on November, 5, 2013.

      8. Agilent Technologies. HaloPlex Target Enrichment System for Illumina sequencing [protocol]. Available at: http://www.chem.agilent.com/Library/usermanuals/Public/G9900-90000.pdf. Accessed on November, 6, 2013.

      9. Illumina Inc. Sequencing: TruSeq amplicon—cancer panel [data sheet]. Available at: http://res.illumina.com/documents/products/datasheets/datasheet_truseq_amplicon_cancer_panel.pdf. Accessed on November, 6, 2013.

      10. Life Technologies. Ion AmpliSeq comprehensive cancer panel. Available at: http://tools.lifetechnologies.com/content/sfs/brochures/Ion_CompCancerPanel_Flyer.pdf. Accessed on November, 6, 2013.

      11. College of American Pathologists. Laboratory general checklist. Available at: http://www.cap.org/apps/docs/laboratory_accreditation/checklists/new/laboratory_general_checklist.pdf. Accessed on November, 6, 2013.

        • Pfeifer J.D.
        • Liu J.
        Rate of occult specimen provenance complications in routine clinical practice.
        Am J Clin Pathol. 2013; 139: 93-100
        • Liu X.
        • Harada S.
        DNA isolation from mammalian samples.
        Curr Protoc Mol Biol. 2013; 102 (2.14.1-2.14.13)
        • Desjardins P.R.
        • Conklin D.S.
        Microvolume quantitation of nucleic acids.
        Curr Protoc Mol Biol. 2011; 93 (A.3J.1-A.3J.16)
        • Gallagher S.R.
        • Desjardins P.R.
        Quantitation of DNA and RNA with absorption and fluorescence spectroscopy.
        Curr Protoc Protein Sci. 2008; 52 (A.4K.1-A.4K.21)
        • Shendure J.A.
        • Porreca G.J.
        • Church G.M.
        • et al.
        Overview of DNA sequencing strategies.
        Curr Protoc Mol Biol. 2011; 96 (7.1.1-7.1.23)
      12. Agilent Technologies. SureSelect target enrichment system for Illumina paired-end sequencing library [protocol]. Available at: http://www.genomics.agilent.com/files/Manual/G3360-90020_SureSelect_Indexing_1.0.pdf. Accessed on May, 21, 2013.

        • Sharma M.K.
        • Phillips J.
        • Agarwal S.
        • et al.
        Clinical genomicist workstation.
        AMIA Summits Transl Sci Proc. 2013; 2013: 156-157
        • Goecks J.
        • Nekrutenko A.
        • Taylor J.
        • Galaxy Team
        Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences.
        Genome Biol. 2010; 11: R86
        • McKenna A.
        • Hanna M.
        • Banks E.
        • et al.
        The Genome Analysis Toolkit: a MapReduce framework for analyzing next generation DNA sequencing data.
        Genome Res. 2010; 20: 1297-1303
        • Ye K.
        • Schulz M.H.
        • Long Q.
        • Apweiler R.
        • Ning Z.
        Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads.
        Bioinformatics. 2009; 25: 2865-2871
        • Li S.
        • Li R.
        • Li H.
        • et al.
        SOAPindel: efficient identification of indels from short paired reads.
        Genome Res. 2013; 23: 195-200
        • O'Rawe J.
        • Jiang T.
        • Sun G.
        • et al.
        Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing.
        Genome Med. 2013; 5: 28
        • Xi R.
        • Lee S.
        • Park P.J.
        A survey of copy-number variation detection tools based on high-throughput sequencing data.
        Curr Protoc Hum Genet. 2012; 75 (7.19.1-7.19.15)
      13. Green RC, Berg JS, Grody WW, et al. ACMG Recommendations for reporting of incidental findings in clinical exome and genome sequencing. American College of Medical Genetics and Genomics 2013. Available at: https://www.acmg.net/docs/ACMG_Releases_Highly-Anticipated_Recommendations_on_Incidental_Findings_in_Clinical_Exome_and_Genome_Sequencing.pdf. Accessed on June, 5, 2013.

        • Gehring N.H.
        • Frede U.
        • Neu-Yilik G.
        • et al.
        Increased efficiency of mRNA 3' end formation: a new genetic mechanism contributing to hereditary thrombophilia.
        Nat Genet. 2001; 28: 389-392
        • Kerr S.E.
        • Thomas C.B.
        • Thibodeau S.N.
        • Ferber M.J.
        • Halling K.C.
        APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests.
        J Mol Diagn. 2013; 15: 31-43
      14. Wellcome Trust Sanger Institute. COSMIC: Catalogue of Somatic Mutations in Cancer. Available at: http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/. Accessed on December 24, 2013.

      15. National Center for Biotechnology Information. dbSNP. Available at: http://www.ncbi.nlm.nih.gov/projects/SNP/. Accessed on December 24, 2013.

      16. National Heart, Lung, and Blood Institute. NHLBI GO Exome Sequencing Project (ESP): Exome Variant Server. Available at: (http://evs.gs.washington.edu/EVS/). Accessed on December 24, 2013.

        • Hsieh Y.Y.
        • Tzeng C.H.
        • Chen M.H.
        • Chen P.M.
        • Wang W.S.
        Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild-type colorectal cancer patients treated with cetuximab-based chemotherapy.
        Cancer Sci. 2012; 103: 791-796
        • Kruger S.
        • Emig M.
        • Lohse P.
        • Ehninger G.
        • Hochhaus A.
        • Schackert H.K.
        The c-kit (CD117) sequence variation M541L, but not N564K, is frequent in the general population, and is not associated with CML in Caucasians.
        Leukemia. 2006; 20 (discussion 356–357): 354-355
        • Whibley C.
        • Pharoah P.D.
        • Hollstein M.
        p53 polymorphisms: cancer implications.
        Nat Rev Cancer. 2009; 9: 95-107
        • Wolf S.M.
        • Annas G.J.
        • Elias S.
        Point-counterpoint. Patient autonomy and incidental findings in clinical genomics.
        Science. 2013; 340: 1049-1050
        • Ladanyi M.
        • Pao W.
        Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond.
        Mod Pathol. 2008; 21: S16-S22
        • Altshuler D.M.
        • Gibbs R.A.
        • Peltonen L.
        • et al.
        • International HapMap Consortium
        Integrating common and rare genetic variation in diverse human populations.
        Nature. 2010; 467: 52-58
        • Abecasis G.R.
        • Altshuler D.
        • Auton A.
        • et al.
        • Genomes Project Consortium
        A map of human genome variation from population-scale sequencing.
        Nature. 2010; 467: 1061-1073
        • Drmanac R.
        • Sparks A.B.
        • Callow M.J.
        • et al.
        Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays.
        Science. 2010; 327: 78-8153
        • Cottrell C.E.
        • Al-Kateb H.
        • Bredemeyer A.J.
        • et al.
        Validation of a next-generation sequencing assay for clinical molecular oncology.
        J Mol Diagn. 2014; 16 (Epub 2013 Nov 6): 89-105https://doi.org/10.1016/j.jmoldx.2013.10.002